918 Short reports

FIG.-Patient at time of presentation, showing ascites.

normal serum bilirubin and no evidence ofhepatocellular
dysfunction or biliary obstruction. Total serum
proteins normal at 8-2 g/100 ml, lipoprotein electro-
phoresis showed a raised B fraction, serum cholesterol
was high at 345 mg/100 ml, and serum triglycerides
increased at 310 mg/100 ml. These abnormally high
values persisted, as did the ascites, after the child's
diabetes was brought under control; and at this stage her
thyroid function was investigated.
Her height at 96 cm was well below the 3rd centile,

though bone age was only marginally less than chrono-
logical age. Serum protein-bound iodine was 3 ,ug/100
ml (normal 4-7 ,ug/100 ml) and serum thyroxine 3-6
jug/100 ml (normal 4-5-13 ug/100 ml). The 4-hour
uptake after 132I (5 iLCi) was 13% (normal range
10-30%/'), but when repeated after administration of 20
units thyroid-stimulating hormone, 4-hour uptake was
only 9-5%. The absence of any extra response to
thyroid-stimulating hormone indicates an absence of
thyroid reserve in the patient. No thyroid antibodies
were shown in either the patient or her mother.

After a diagnosis of hypothyroidism, her progress on a
small dose of thyroxine (0 025 mg daily) has been
encouraging. She has grown 3 cm in 6 months, ascites
and abdominal distension are no longer evident, and her
skin and hair are less dry and coarse. Her mother
reports she is generally more lively and interested.

Discussion
This case is presented not only because the

combination of Down's syndrome with diabetes
mellitus and hypothyroidism is rare, but also
because of the unusual presentation of this child's
disturbance of thyroid function.
Thyroid function in Down's syndrome is usually

normal (Marks and Hamlin, 1967), but both
hyperthyroidism (Kurland et al., 1957) and

hypothyroidism have been described. The latter is
less common, and until 1965 only 5 cases had been
reported (Hayles, Hinrichs, and Tauxe, 1965).
The triple combination of hypothyroidism,

Down's syndrome, and diabetes mellitus is even
more rare and there are only two previously
described cases (Daniels and Simon, 1968; Litman,
1968), who were aged 13 months and 17 years at the
time the full picture became evident.

Investigations in this child have shown that she
was hypothyroid rather than totally deficient in
thyroid function. The presenting symptom of
ascites is unusual in children, but fluid accumulation
in the peritoneum and elsewhere is a well-recognized
clinical feature of adult myxoedema. On admission
the provisional diagnosis in this case was Mauriac
syndrome (Guest, 1953), but it is doubtful if this
condition of hepatomegaly, stunting of growth, and
poorly controlled diabetes mellitus is an entity.
Rather, this patient shows a rare cause of that
unusual condition.

Summary
A child with Down's syndrome who subsequently

developed diabetes mellitus and hypothyroidism
before the age of 6 years is described. The
principal presenting feature of her disturbed thyroid
function was ascites.

REFERENCES

Daniels, D. M., and Simon, J. L. (1968). Down's syndrome,
hypothyroidism, and diabetes mellitus. Journal of Pediatrics,
72, 697.

Guest, G. M. (1953). The Mauriac syndrome. Diabetes, 2, 415.
Hayles, A. B., Hinrichs, W. L., and Tauxe, W. N. (1965). Thyroid

disease among children with Down's syndrome (mongolism).
Pediatrics, 36, 608.

Kurland, G. S., Fishman, J., Hamolsky, M. W., and Freedberg, A. S.
(1957). Radioisotope study of thyroid function in 21 mongoloid
subjects, including observations in 7 parents. Journal of
Clinical Endocrinology, 17, 552.

Litman, N. N. (1968). Down's syndrome, hypothyroidism, and
diabetes mellitus. Journal of Pediatrics, 73, 798.

Marks, J. F., and Hamlin, M. (1967). Free thyroxine levels in
children with mongolism. Journal of Pediatrics, 70, 435.

W. ABDEL SHAHEED and L. ROSENBLOOM*
Royal Liverpool Children's Hospital, Liverpool.

*Correspondence to Dr. L. Rosenbloom, Alder Hey Children's
Hospital, Eaton Road, Liverpool L12 2AP.

Cartilage hair hypoplasia
Cartilage hair hypoplasia was first described by

McKusick in 1964. While studying the old Amish
sect he noticed an association between short-limbed
dwarfism and sparseness of hair, and later reported

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Short reports
77 cases (McKusick et al., 1965). Since then several
cases with no Amish ancestry have been published.
However, though two variants of this rare condition
were shown in Britain recently (Savage, 1972),
no other cases have been published in Britain.

Case report
A male was the product of the third pregnancy of a

young mother. There was no history of consanguinity
in the parents and, apart from hydramnios, the pregnancy
had been normal.
He weighed 2 - 77 kg (1Oth centile) at birth, and crown

to heel length was 43 cm (below the 3rd centile). An
oesophageal tube was passed without difficulty into the
stomach. Both upper and lower limbs were short in
relation to the trunk, but there was no clinical or
radiological evidence of achondroplasia.
At 3 weeks of age he was admitted to the Radcliffe

Infirmary with large intestinal obstruction, which was
relieved by sigmoid colostomy. A biopsy showed
Hirschsprung's disease and at 9 months of age the
aganglionic segment was resected and the colostomy
closed (Mr. Malcolm Gough).
At 2N years of age he was readmitted for assessment of

his short stature and particularly for investigations
appropriate to the cartilage hair hypoplasia syndrome,
which seemed a likely diagnosis. His height remained
below the third centile and his weight had fallen below
this level, falling away from the centile lines.
On examination he was strikingly short, height 76 cm

and weight 12 8 kg. He had very fine and sparse fair
hair, and the lower limbs appeared disproportionately
shorter than the upper limbs (Fig. 1). His hands were

FIG. 1.-The patient aged 21 years. Note increased
lumbar lordosis and fine sparse hair.

short and broad, and it was not possible to extend fully
either elbow. The sternum was abnormally prominent,
and there was marked bowing of the legs. No hyper-
extensibility of the joints could be shown. His

919
intellectual development was considered to be within
normal limits for his age.

Investigations.
X-rays. The skeleton showed generalized changes of

typical metaphyseal dysostosis, i.e. widening, cupping,
and defective mineralization in the metaphyses of the
tubular bones (Fig. 2).

FIG. 2.-X-ray of left lower limb of patient showing
widening, cupping, and defective mineralization of the

metaphvses.

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920 Short reports
Hair. Amino acid analysis of the scalp hair (Dr. R. J.

Pollitt) gave normal results. Electron microscopical
examination (Dr. R. P. R. Dawber) showed that the
majority of the hairs had a diameter approximately i of
normal, but the cuticular scale pattern was within normal
limits.

Biochemical. The following were performed with
normal results: lipid tolerance test, microscopical
examination for fat globules in stools, blood urea and
electrolytes, urinary amino acid chromatography, and
mucopolysaccharide screening test.

Discussion
The main features of the syndrome are (i) short

limbed dwarfism with bow legs and increased
lumbar lordosis; (ii) minor skeletal abnormalities of
anterior protrusion of the sternum, hyper-
extensibility of joints, limitation of extension of
elbows; (iii) fine sparse hair; and (iv) autosomal
recessive inheritance. Associated features in some
patients are Hirschsprung's disease, malabsorption
syndrome, and poor resistance to some virus
infections.

Skeletal disorder. Cartilage hair hypoplasia is
one of several disorders in which the abnormality of
the growth plate known as metaphyseal dysostosis
leads to short stature (Irwin, 1966). The other 3
main disorders are (1) Jansen type; rare; associated
with mental and motor retardation; pattern of
inheritance unknown. (2) Schmidt type; dwarfism
mild; skeletal deformities slight; intelligence
average; an autosomal dominant. (3) Spahr type;
similar to Schmidt type but an autosomal recessive.
Thus cartilage hair hypoplasia differs from these
disorders in the markedly short stature, and differs
from the Jansen type in the absence of severe
intellectual deficit.
The localized skeletal abnormalities present in

cartilage hair hypoplasia (Smith, 1970), i.e. short
broad hands, lack of full extension of elbow joints,
prominence of the sternum with flaring of the bony
rib cage, bow legs, and increased lumbar lordosis,
may be present in the other varieties.

Hair. The other striking feature which
distinguishes this from the other types of meta-
physeal dysostosis is the very short, fine, sparse
scalp hair. Coupe and Lowry (1970) have analysed
hair from typical cases and found a normal amino
acid content, but a thin structure with lower tensile
strength and the lack of a central pigment core,
which is present in normal hair. The hair from our
patient shows the first two features.

Associated alimentary tract disorders. In
the report of McKusick et al. (1965) one of the 77
patients died of coeliac disease and in 5 others
malabsorption was suspected. There was no
evidence of malabsorption in our patient, though
full investigation to exclude this was not carried out.
Two of McKusick's patients had Hirschsprung's
disease, which was the presenting feature in our
case.

Associated severe viral infections. 2 of
McKusick's patients died of chickenpox and 3 others
were so severely affected that a diagnosis of smallpox
was seriously considered. Lux et al. (1970)
extensively investigated 2 children with cartilage
hair hypoplasia who had severe varicella and found
them to have chronic neutropenia and disordered
cellular immunity. Burke et al. (1967) mentioned 2
patients with exocrine pancreatic insufficiency and
neutropenia who had metaphyseal dysostosis (Cases
5 and 11) and one who had Hirschsprung's disease.
No mention was made of the state of the hair.
Our patient has so far had no clinical evidence of a

poor response to infection.
This is another of the many rare genetic disorders

in which correct diagnosis is advantageous to the
patient and his family even though the condition
itself is untreatable, as the parents can be informed
of the poor prognosis for linear growth but the fairly
good prognosis for intellectual development, and the
genetic implications for further sibs can be
explained. The physician will be aware of the
possibility of malabsorption, Hirschsprung's disease,
and severe illness with viral infection.

Summary
A patient with cartilage hair hypoplasia associated

with Hirschsprung's disease is described. The
syndrome is a rare cause of short-limbed dwarfism,
and is inherited as an autosomal recessive. Apart
from small stature, the main features are fine, sparse
scalp hair and characteristic radiological changes of
metaphyseal dysostosis.

We are grateful to Drs. R. J. Pollitt (University of
Sheffield, Department of Psychiatry), R. P. R. Dawber
(St. John's Hospital for Diseases ofthe Skin), T. J. Ryan,
Consultant Dermatologist, and J. C. McLamon,
Consultant Radiologist (United Oxford Hospitals) for
their help; and thank Mr. Malcolm Gough, Consultant
Surgeon (United Oxford Hospitals) for information on
the surgical aspects of this patient.

REFERENCES
Burke, V., Colebatch, J. H., Anderson, C. M., and Simons, M. J.

(1967). Association of pancreatic insufficiency and chronic
neutropenia in childhood. Archives of Disease in Childhood, 42,
147.

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Short reports 921
Coupe, R. L., and Lowry, R. B. (1970). Abnormality of the hair in

cartilage-hair hypoplasia. Dermatologica, 141, 329.
Irwin, G. A. L. (1966). Cartilage-hair hypoplasia (CHH) variant of

familial metaphyseal dysostosis. Radiology, 86, 926.
Lux, S. E., Johnston, R. B., August, C. S., Say, B., Penchaszadeh, V.

B., Rosen, F. S., and McKusick, V. A. (1970). Chronic
neutropenia and abnormal cellular immunity in cartilage-hair
hypoplasia. New England Journal of Medicine, 282, 231.

McKusick, V. A. (1964). Metaphyseal dysostosis and thin hair; a
'new' recessively inherited syndrome ? Lancet, 1, 832.

McKusick, V. A., Eldridge, R., Hostetler, J. A., Ruangwit, U., and
Egeland, J. A. (1965). Dwarfism in the Amish. II.
Cartilage-hair hypoplasia. Bulletin of the Johns Hopkins
Hospital, 116, 285.

Savage, M. 0. (1972). Metaphyseal dysplasia in siblings: a variant
of cartilage-hair hypoplasia. Proceedings of the Royal Society of
Medicine, 65, 727.

Smith, D. W. (1970). Recognizable Patterns of Human Mal-
formation, p. 204. Saunders, Philadelphia and London.

C. B. BooTHBY* and B. D. BOWER
Department of Paediatrics, Radcliffe Infirmary,
Oxford.

*Correspondence to Dr. C. B. Boothby, West Suffolk General
Hospital, Bury St. Edmunds, Suffolk IP33 3JX.

The following articles will appear in future issues of this journal:

Looking back: Bray's discovery of pathogenic Esch. coli as a cause of infantile gastroenteritis. J. Bray.
Personal comment: Paediatrics and child psychiatry: the case for collaboration. P. Pinkerton.
Assessment of techniques for measurement of blood pressure in infants and children. A. M. Elseed, E. A.
Shinebourne, and M. C. Joseph.
Exercise-induced bronchial lability and atopic status of families of infants with wheezy bronchitis. P. Konig and
S. Godfrey.
Sex chromosome aberrations and speech development. M. Garvey and D. E. Mutton.
Serum protein and transferrin determinations to distinguish kwashiorkor from iron deficiency anaemia. A. E. J.
Masawe and J. Rwabwogo-Atenyi.
Diaphragmatic paralysis in the newborn. D. Anagnostakis, E. Economou-Mavrou, A. Moschos, P. Vlachos, and
D. Liakakos.
Treatment with new synthetic analogue of vasopressin in diabetes insipidus. H. Nash.

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